Epidermal cells and fibroblasts will be separately cultured from skin biopsies from cystic fibrosis patients, normal controls and obligate heterozygotes. A detailed comparison of proteins synthesized by the cystic fibrosis and normal cells of each type will be carried out by two-dimensional polyacrylamide gel electrophoresis, using double-label autoradiography to compare each cystic fibrosis sample with a control sample on the same gel. The survey will include basic and acidic proteins. If differences are found tha correlate well with the cystic fibrosis state, we will determine whether the differences involve glycoproteins, using radioactive sugars as precursors. Our principal goal is to identify differences which, when fully characterized in later studies, will be helpful in elucidating the primary biochemical defect in cystic fibrosis. We will also search for differences that may distinguish heterozygotes from homozygous normals.